A first in sperm research

Professors Martyn Paley and Allan Pacey of the University of Sheffield published their late last month in the journal Molecular Human Reproduction.

They said their technique, magnetic resonance spectroscopy (MRS), is the first to successfully examine and measure molecules in live sperm.

Using powerful magnets, MRS works like radar. It fires low-energy pulses at a sperm sample inside a specially designed scanner, which listens to the response of the molecules to the echoed signal.

This, the scientists said, could help to distinguish between populations of good or poor sperm.

Pacey, PhD, fertility expert, and professor of andrology in Sheffield’s Academic Unit of Reproductive and Developmental Medicine, said their study is the first to show that it is possible to use MRS to obtain information about the molecules and metabolites in live human spermatozoa.

“To achieve this, we needed to develop a reliable method to recover sperm from seminal plasma — the fluid in which they are ejaculated — while remaining certain that the MRS signals were only being obtained from sperm,” Pacey told Healthline.

Paley, PhD, professor of bio-medical imaging in the university’s Department of Infection, Immunity and Cardiovascular Disease, said that MRS has been used before to examine the molecular composition of many cells and tissues in other diseases such as cancer, but it has never previously been used to examine live sperm.

A measuring technique

Pacey used a variety of sperm washing methods that are commonly used to prepare sperm for assisted conception procedures, such as in vitro fertilization (IVF).

They found that a washing step, called density gradient centrifugation, was the best way to prepare sperm for scanning.

How did scientists measure molecules in live sperm before this breakthrough?

“They didn’t,” Pacey said. “Previously, the only way to examine the molecules in sperm was to use a proteomic approach. That means the sperm must be killed and broken open.”

Previously, scientists also looked at sperm using MRS after the sperm had been killed and the molecules put in solution, using methanol extraction, he said.

“Both are excellent and sensitive techniques,” he said. “But the disadvantage is that it’s not then possible to do anything else with the sperm afterward. In our method, however, the sperm are still alive and potentially could be used in a fertility treatment such as IVF, although we have not done that yet.”

In a study published in September 2012, in the journal Human Reproduction, Pacey concluded that common lifestyle choices make little contribution to the risk of low motile sperm concentration (MSC). Motility measures how well sperm move.

In their new study, Pacey and Paley tested sperm from healthy men and from others with fertility problems.

They sampled one ejaculate per man from 37 healthy volunteers. Each ejaculate contained millions of sperm. The researchers then tested their method on 20 semen samples from men undergoing fertility assessment.

“The men were between 18 and about 40, although age is not very important in this study,” Pacey said. “There are only minor changes in ejaculate quality with increasing age, and they are not that clinically significant. Men can father children into old age if their partner is still in her fertile years. For example, actor Charlie Chaplin was 73 when he fathered his 11th child with his fourth wife.”

Overcoming technical challenges

From their collected data, the scientists built a profile of the molecules present in the sperm and how they differed between samples.

The research team faced technical difficulties when they tried to distinguish the molecules present in sperm from those occurring in semen, the fluid in which sperm are ejaculated.

Pacey said they explored several sperm washing methods that are used to prepare sperm for IVF. By spinning the samples quickly several times in a centrifuge, they could reduce the background “noise” from molecules in semen to accurately differentiate them from the molecules in sperm.

“The problem to date is that the measures we have to assess sperm health were developed in the 1950s,” Pacey said. “Although there have been many attempts to improve on these tests, none has so far entered clinical practice. Moreover, they are all destructive to sperm. So, we hope that we might be able to identify a simple biomarker that might be a useful addition to the current tests, or even one day replace them.”

Can research help in a clinical setting?

One physician specializing in fertility said additional research will be needed before these new findings can have clinical usefulness.

Dr. Bobby Najari is a urologist, and assistant professor of urology at New York University Langone Medical Center, who specializes in male infertility and sexual health. He said that while the Sheffield study describes a proof of principle, more work needs to be done to evaluate whether MRS will have clinical implications.

“The authors clearly outline many of the limitations that need to be overcome for this to be used clinically,” Najari told Healthline.

“Those include the fact that the supportive media that sperm are typically stored in would interfere with the MRS technology. But more importantly, the investigators ultimately need to determine whether the information provided by MRS adds clinical value beyond the standard density-gradient technique, and whether the process of MRS itself negatively impacts the health of sperm.”

Evaluating the damage to the DNA carried by sperm would be a technique with more clinical application, he said, since ultimately this is the contribution of the sperm to the embryo.

“Sperm DNA can be evaluated through a variety of methods,” Najari said. “However, they all render the evaluated sperm unusable for assisted reproductive techniques. Thus, they are diagnostic tests that can guide therapy, but they can’t be used to select individual sperm that will be used in assisted reproductive technology.”

The future value of this new research is unclear, he said. “It really needs to be tied to clinical outcomes, and it needs to demonstrate that it gives us useful information beyond what it already used.”

Pacey is optimistic about the future use of their research.

“Our hope is that it might help find a biomarker to help with diagnosis of male fertility,” he said. “Or it could help find potential therapy targets which might improve how sperm swim and thereby avoid the need for men to undergo assisted conception with their partner.”